Research Interests

The research in my lab focuses principally on identifying the molecular mechanisms by which normal cells in the tumor microenvironment contribute to tumor growth and spread. We have published extensively on molecular mechanisms regulating tumor angiogenesis and lymphangiogenesis. Our work in recent times has turned to focus on the role of innate immune cells, including granulocytes, monocytes, macrophages and so-called myeloid derived suppressor cells in the regulation of tumor growth and angiogenesis. We recently described a key role for PI3Kinase gamma in the regulation of monocyte trafficking to tumors and their subsequent promotion of tumor growth and metastasis. We found that tumor derived growth factors, cytokines and chemokines activate integrin a4b1 to promote myeloid cell adhesion to vascular endothelium in tumors. This activation event requires a series of steps leading to conformational changes in integrin a4b1 and depend on PI3kinase gamma activation of the small GTPase Rap1. We furthermore are characterizing the regulation of the M1 vs M2 macrophage phenotype by PI3kinase gamma and studying the role of macrophages in tumor angiogenesis, lymphangiogenesis and fibrosis.